Relative Sea-Level Rise and Potential Submersion Risk for 2100 on 16 Coastal Plains of the Mediterranean Sea.

The coasts of the Mediterranean Sea are dynamic habitats in which human activities have been conducted for centuries and which feature micro-tidal environments with about 0.40 m of range. For this reason, human settlements are still concentrated along a narrow coastline strip, where any change in the sea level and coastal dynamics may impact anthropic activities. In the frame of the RITMARE and the Copernicus Projects, we analyzed light detection and ranging (LiDAR) and Copernicus Earth Observation data to provide estimates of potential marine submersion for 2100 for 16 small-sized coastal plains located in the Italian peninsula and four Mediterranean countries (France, Spain, Tunisia, Cyprus) all characterized by different geological, tectonic and morphological features. The objective of this multidisciplinary study is to provide the first maps of sea-level rise scenarios for 2100 for the IPCC RCP 8.5 and Rahmstorf (2007) projections for the above affected coastal zones, which are the locations of touristic resorts, railways, airports and heritage sites. On the basis of our model (eustatic projection for 2100, glaciohydrostasy values and tectonic vertical movement), we provide 16 high-definition submersion maps. We estimated a potential loss of land for the above areas of between about 148 km(2)(IPCC-RCP8.5 scenario) and 192 km(2)(Rahmstorf scenario), along a coastline length of about 400 km

Whole genome experimental maps of DNA G-quadruplexes in multiple species.

Genomic maps of DNA G-quadruplexes (G4s) can help elucidate the roles that these secondary structures play in various organisms. Herein, we employ an improved version of a G-quadruplex sequencing method (G4-seq) to generate whole genome G4 maps for 12 species that include widely studied model organisms and also pathogens of clinical relevance. We identify G4 structures that form under physiological K+ conditions and also G4s that are stabilized by the G4-targeting small molecule pyridostatin (PDS). We discuss the various structural features of the experimentally observed G-quadruplexes (OQs), highlighting differences in their prevalence and enrichment across species. Our study describes diversity in sequence composition and genomic location for the OQs in the different species and reveals that the enrichment of OQs in gene promoters is particular to mammals such as mouse and human, among the species studied. The multi-species maps have been made publicly available as a resource to the research community. The maps can serve as blueprints for biological experiments in those model organisms, where G4 structures may play a role.The S.B. research group is supported by programme grant funding from Cancer Research UK (C9681/A18618), European Research Council Advanced Grant No. 339778, a Wellcome Trust Senior Investigator Award (grant 209441/z/17/z) and by core funding from Cancer Research UK (C14303/A17197). We are grateful to the Biotechnology and Biological Sciences Research Council (BBSRC) and Illumina for the CASE studentship supporting V.S.C. (BB/I015477/1)

G-quadruplex DNA structures in human stem cells and differentiation.

Funder: Herchel Smith FundsThe establishment of cell identity during embryonic development involves the activation of specific gene expression programmes and is underpinned by epigenetic factors including DNA methylation and histone post-translational modifications. G-quadruplexes are four-stranded DNA secondary structures (G4s) that have been implicated in transcriptional regulation and cancer. Here, we show that G4s are key genomic structural features linked to cellular differentiation. We find that G4s are highly abundant in human embryonic stem cells and are lost during lineage specification. G4s are prevalent in enhancers and promoters. G4s that are found in common between embryonic and downstream lineages are tightly linked to transcriptional stabilisation of genes involved in essential cellular functions as well as transitions in the histone post-translational modification landscape. Furthermore, the application of small molecules that stabilise G4s causes a delay in stem cell differentiation, keeping cells in a more pluripotent-like state. Collectively, our data highlight G4s as important epigenetic features that are coupled to stem cell pluripotency and differentiation

Petrarca e l'Umanesimo latino

[Atti del convegno AlmaPetrarca V edizione (Bologna 15 marzo 2022)] I saggi qui raccolti mettono in dialogo opere e fonti petrarchesche con testi e autori successivi, si interrogano ancora una volta sul metodo di lavoro petrarchesco e tentano di esplorare l’incessante colloquio fra Petrarca e gli umanisti. La scelta di concentrare l’indagine sull’Umanesimo latino muove dalla necessità di stimolare una nuova lettura di alcune opere tutt’altro che secondarie nella produzione del poeta aretino: in alcuni contributi, infatti, si mettono in luce le riflessioni del Petrarca autoesegeta, mentre in altri vengono approfonditi i tempi, i luoghi e le forme della ricezione dei modelli petrarcheschi. Il risultato è un volume miscellaneo che da un lato arricchisce la non esigua bibliografia degli studi e dall’altro apre il campo a nuove indagini e nuovi spunti per la ricerca futura

Tracheal and major bronchial injuries

Tracheobronchial injuries are rare but potentially life threatening. Their manifestations are variable and protean and misdiagnoses are common. Successful diagnosis and treatment often require a high level of suspection and unique surgical repairs to a given injury. Tracheal and main bronchial disruptions usually occurs after blunt chest trauma in the vicinity of the carina. Tracheobronchial disruptions occurred associated with high-energy impact trauma, and associated injuries were more common than they were to occur alone. Common presenting signs included subcutaneous emphysema, dyspnea, sternal tenderness, and hemoptysis. The most common were radiographic findings pneumothorax, pneumomediastinum, and clavicle or rib fractures. Rigid bronchoscopy and fiberoptic bronchoscopy were both highly accurate for the diagnosis but only when performed by trained thoracic surgeons. Emphasis has been placed on the importance of early diagnosis, to avoid the complications associated with a delayed repair. The etiological mechanisms, diagnostic and therapeutic aspects are reviewed and discussed.As lesões traqueobrônquicas são raras, porém, no trauma de tórax, envolvem grande risco de vida. As suas manifestações são variáveis e não é incomum o diagnóstico ser protraído. O sucesso no diagnóstico e tratamento, freqüentemente, requer alto grau de suspeição e a correção cirúrgica como método de escolha. Após trauma fechado de tórax, a ruptura da traquéia e dos brônquios principais, geralmente, ocorre nas proximidades da carina. O rompimento da árvore traqueobrônquica, ocasionado por acidentes em alta velocidade, com alto impacto e grande liberação de energia, geralmente está associado a outras lesões. Os sinais comumente presentes são: enfisema subcutâneo, dispnéia e hemoptise. Os achados radiológicos mais comuns incluem pneumotórax, pneumomediastino, fraturas de costelas e clavícula. As broncoscopias efetivamente rígida e flexível são considerados métodos diagnósticos eficazes, desde que manuseados por cirurgião torácico treinado. O diagnóstico precoce deve ser enfatizado, pois evita as complicações associadas ao reparo tardio das lesões. O mecanismo etiológico, o diagnóstico e os aspectos da terapêutica na literatura mundial são revistos e discutidos

Machine learning model for sequence-driven DNA G-quadruplex formation.

We describe a sequence-based computational model to predict DNA G-quadruplex (G4) formation. The model was developed using large-scale machine learning from an extensive experimental G4-formation dataset, recently obtained for the human genome via G4-seq methodology. Our model differentiates many widely accepted putative quadruplex sequences that do not actually form stable genomic G4 structures, correctly assessing the G4 folding potential of over 700,000 such sequences in the human genome. Moreover, our approach reveals the relative importance of sequence-based features coming from both within the G4 motifs and their flanking regions. The developed model can be applied to any DNA sequence or genome to characterise sequence-driven intramolecular G4 formation propensities

Environmental toxins trigger PD-like progression via increased alpha-synuclein release from enteric neurons in mice

Pathological studies on Parkinson’s disease (PD) patients suggest that PD pathology progresses from the enteric nervous system (ENS) and the olfactory bulb into the central nervous system. We have previously shown that environmental toxins acting locally on the ENS mimic this PD-like pathology progression pattern in mice. Here, we show for the first time that the resection of the autonomic nerves stops this progression. Moreover, our results show that an environmental toxin (i.e. rotenone) promotes the release of alpha-synuclein by enteric neurons and that released enteric alpha-synuclein is up-taken by presynaptic sympathetic neurites and retrogradely transported to the soma, where it accumulates. These results strongly suggest that pesticides can initiate the progression of PD pathology and that this progression is based on the transneuronal and retrograde axonal transport of alpha-synuclein. If confirmed in patients, this study would have crucial implications in the strategies used to prevent and treat PDThis work was supported by the Fritz-Thyssen Foundation, theGerman Parkinson’s disease Society and by Amelia Jimenez Gomez as private dono

Landscape of G-quadruplex DNA structural regions in breast cancer.

Response and resistance to anticancer therapies vary due to intertumor and intratumor heterogeneity1. Here, we map differentially enriched G-quadruplex (G4) DNA structure-forming regions (∆G4Rs) in 22 breast cancer patient-derived tumor xenograft (PDTX) models. ∆G4Rs are associated with the promoters of highly amplified genes showing high expression, and with somatic single-nucleotide variants. Differences in ΔG4R landscapes reveal seven transcription factor programs across PDTXs. ∆G4R abundance and locations stratify PDTXs into at least three G4-based subtypes. ∆G4Rs in most PDTXs (14 of 22) were found to associate with more than one breast cancer subtype, which we also call an integrative cluster (IC)2. This suggests the frequent coexistence of multiple breast cancer states within a PDTX model, the majority of which display aggressive triple-negative IC10 gene activity. Short-term cultures of PDTX models with increased ∆G4R levels are more sensitive to small molecules targeting G4 DNA. Thus, G4 landscapes reveal additional IC-related intratumor heterogeneity in PDTX biopsies, improving breast cancer stratification and potentially identifying new treatment strategies.The Caldas and Balasubramanian laboratories are supported by core funding from Cancer Research UK (C14303/A17197). The Balasubramanian laboratory is supported by Program grant funding from Cancer Research UK (C9681/A18618 and C9681/A29214) and a Wellcome Trust Investigator Award (209441/z/17/z). Prior to the revision of this study work by Dr. Robert Hänsel-Hertsch was supported by the Balasubramanian group, afterwards additionally supported by core funding of the Center for Molecular Medicine Cologne (CMMC)